Evidence has now accumulated demonstrating that a number of streptococcal antigens share antigenic determinants with a variety of host tissues. Interest has centered around those cross reactions which involve cardiac tissue and what role they may play in the initiation and perpetuation of the disease, rheumatic fever. Some of these cross reactions are in the streptococcal cell wall while others are antigens within the streptococcal membrane moiety. The finding that those individuals susceptible to contracting rheumatic fever have a genetic marker present on their B cells raises the interesting question whether these individuals are genetically programmed to respond abnormally to these cross reactive antigens and what role this B cell alloantigen might play in the disease process. It is the aim of this proposal to study these microbial host interactions as follows: 1) Using monoclonal antibody (D8/17) which identifies a B cell antigen in rheumatics, we will study the frequency of this antigen in rheumatic fever patients and their families as well as control and nephritic patients. Special attention will be paid to the relationship of this marker to other markers of the MHC complex. 2) To define the molecular structure of this antigen and to determine whether it is present in other tissues. 3) To determine what role this B cell marker plays in the immune response to streptococcal antigens in rheumatic and non rheumatic individuals. 4) To further investigate the nature of the antigen(s) in the immune complexes in ARF patients. 5) Finally we will continue to isolate and characterize those cardiac antigens which cross react with strepococcal antigens. Since rheumatic fever is one of the few rheumatic diseases in which we know the inciting agent, further knowledge concerning this microbial-host interaction has obvious implications for other immunologically mediated rheumatic diseases in which an agent is presumed but not proven.